Alverine

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Alverine
Alverine.png
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Identifiers
  • N-Ethyl-3-phenyl-N-(3-phenylpropyl)propan-1-amine
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Chemical and physical data
Formula C20H27N
Molar mass 281.443 g·mol−1
3D model (JSmol)
  • c1ccccc1CCCN(CC)CCCc2ccccc2
  • InChI=1S/C20H27N/c1-2-21(17-9-15-19-11-5-3-6-12-19)18-10-16-20-13-7-4-8-14-20/h3-8,11-14H,2,9-10,15-18H2,1H3 Yes check.svgY
  • Key:ZPFXAOWNKLFJDN-UHFFFAOYSA-N Yes check.svgY
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Alverine is a drug used for functional gastrointestinal disorders. Alverine is a smooth muscle relaxant. Smooth muscle is a type of muscle that is not under voluntary control; it is the muscle present in places such as the gut and uterus.

Contents

Adverse effects

The side effects of alverine include: [1] [2]

It was reported that alverine may induce toxic hepatitis. [3] [4]

Mechanism of action

Alverine acts directly on the muscle in the gut, causing it to relax. Alverine is a 5HT1A antagonist, which reduces rectal hypersensitivity. [5] This prevents the muscle spasms which occur in the gut in conditions such as irritable bowel syndrome and diverticular disease. [6] Diverticular disease is a condition in which small pouches form in the gut lining. These pouches can trap particles of food and become inflamed and painful. In irritable bowel syndrome, the normal activity of the gut muscle is lost. The muscle spasms result in symptoms such as abdominal pain and bloating, constipation or diarrhoea. By relaxing the gut muscle, alverine citrate relieves the symptoms of this condition. Alverine also relaxes the smooth muscle in the womb (uterus). It is therefore also used to treat painful menstruation, which is caused by muscle spasms in the uterus (dysmenorrhea).

Alverine capsules [7] are now available in the market. There are two strengths of capsule - 60 mg and 120 mg. The common dosage for adults and children over 12 years is 60–120 mg taken one, two or three a day, either before or after meals. Alverine is not suitable for those aged under 12 years. Women who are pregnant or breast-feeding should follow the instruction of doctors for the drug.

Development and marketing

A combination of alverine citrate and simeticone (ACS) for irritable bowel syndrome therapy were compared with placebo in a phase IV clinical trial. [8] At week 4, the alverine citrate and simeticone group had lower VAS scores for abdominal pain/discomfort (median: 40 mm vs. 50 mm, P = 0.047) and higher responder rate (46.8% vs. 34.3%, OR = 1.3; P = 0.01) as compared with the placebo group. [9]

The drug was firstly authorized for marketing on 03/06/2014. The marketing authorisation holder is Dr. Reddy's Laboratories (UK) Ltd. [10]

Related Research Articles

<span class="mw-page-title-main">Defecation</span> Expulsion of feces from the digestive tract

Defecation follows digestion, and is a necessary process by which organisms eliminate a solid, semisolid, or liquid waste material known as feces from the digestive tract via the anus or cloaca. The act has a variety of names ranging from the common, like pooping or crapping, to the technical, e.g. bowel movement, to the obscene (shitting), to the euphemistic, to the juvenile. The topic, usually avoided in polite company, can become the basis for some potty humor.

<span class="mw-page-title-main">Irritable bowel syndrome</span> Functional gastrointestinal disorder

Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain, abdominal bloating and changes in the consistency of bowel movements. These symptoms may occur over a long time, sometimes for years. IBS can negatively affect quality of life and may result in missed school or work or reduced productivity at work. Disorders such as anxiety, major depression, and chronic fatigue syndrome are common among people with IBS.

An antispasmodic is a pharmaceutical drug or other agent that suppresses muscle spasms.

<span class="mw-page-title-main">Abdominal pain</span> Stomach aches

Abdominal pain, also known as a stomach ache, Is a symptom associated with both non-serious and serious medical issues. Since the abdomen contains most of the body's vital organs, it can be an indicator of a wide variety of diseases. Given that, approaching the examination of a person and planning of a differential diagnosis is extremely important.

Functional gastrointestinal disorders (FGID), also known as disorders of gut–brain interaction, include a number of separate idiopathic disorders which affect different parts of the gastrointestinal tract and involve visceral hypersensitivity and motility disturbances.

<span class="mw-page-title-main">Diverticular disease</span> Medical condition

Diverticular disease is when problems occur due to diverticulosis, a benign condition defined by the formation of pouches (diverticula) from the weak spots in the wall of the large intestine. This disease spectrum includes diverticulitis, symptomatic uncomplicated diverticular disease (SUDD), and segmental colitis associated with diverticulosis (SCAD). The most common symptoms across the disease spectrum are abdominal pain and bowel habit changes such as diarrhea or constipation. Otherwise, diverticulitis presents with systemic symptoms such as fever and elevated white blood cell count whereas SUDD and SCAD don’t. Treatment ranges from conservative bowel rest to medications such as antibiotics, antispasmodics, acetaminophen, mesalamine, rifaximin, and corticosteroids depending on the specific conditions.

<span class="mw-page-title-main">Renzapride</span> Chemical compound

Renzapride is a prokinetic agent and antiemetic which acts as a full 5-HT4 agonist and partial 5-HT3 antagonist. It also functions as a 5-HT2B antagonist and has some affinity for the 5-HT2A and 5-HT2C receptors.

<span class="mw-page-title-main">Rifaximin</span> Antibiotic medication

Rifaximin, is a non-absorbable, broad spectrum antibiotic mainly used to treat travelers' diarrhea. It is based on the rifamycin antibiotics family. Since its approval in Italy in 1987, it has been licensed in over more than 30 countries for the treatment of a variety of gastrointestinal diseases like irritable bowel syndrome, and hepatic encephalopathy. It acts by inhibiting RNA synthesis in susceptible bacteria by binding to the RNA polymerase enzyme. This binding blocks translocation, which stops transcription. It is marketed under the brand name Xifaxan by Salix Pharmaceuticals.

The Rome process and Rome criteria are an international effort to create scientific data to help in the diagnosis and treatment of functional gastrointestinal disorders, such as irritable bowel syndrome, functional dyspepsia and rumination syndrome. The Rome diagnostic criteria are set forth by Rome Foundation, a not for profit 501(c)(3) organization based in Raleigh, North Carolina, United States.

<span class="mw-page-title-main">Mebeverine</span> Chemical compound

Mebeverine is a drug used to alleviate some of the symptoms of irritable bowel syndrome. It works by relaxing the muscles in and around the gut.

<span class="mw-page-title-main">Lubiprostone</span> Medication used for constipation

Lubiprostone, sold under the brand name Amitiza among others, is a medication used in the management of chronic idiopathic constipation, predominantly irritable bowel syndrome-associated constipation in women and opioid-induced constipation. The drug is owned by Mallinckrodt and is marketed by Takeda Pharmaceutical Company.

<span class="mw-page-title-main">Polycarbophil calcium</span> Pharmaceutical drug

Polycarbophil calcium (INN) is a drug used as a stool stabilizer. Chemically, it is a synthetic polymer of polyacrylic acid cross-linked with divinyl glycol, with calcium as a counter-ion.

<span class="mw-page-title-main">Mosapride</span> Chemical compound

Mosapride is a gastroprokinetic agent that acts as a selective 5HT4 agonist. The major active metabolite of mosapride, known as M1, additionally acts as a 5HT3 antagonist, which accelerates gastric emptying throughout the whole of the gastrointestinal tract in humans, and is used for the treatment of gastritis, gastroesophageal reflux disease, functional dyspepsia and irritable bowel syndrome. It is recommended to be taken on an empty stomach (i.e. at least one hour before food or two hours after food).

Solabegron is a drug which acts as a selective agonist for the β3 adrenergic receptor. It is being developed for the treatment of overactive bladder and irritable bowel syndrome. It has been shown to produce visceral analgesia by releasing somatostatin from adipocytes.

Otilonium bromide, sold under the trade name Spasmomen among others, is an antimuscarinic and calcium channel blocker used to relieve spasmodic pain of the gut, especially in irritable bowel syndrome. This means it works in the gut themselves, by relaxing the small muscles of the intestines, which results in relieving cramps and therefore reduces pain.

<span class="mw-page-title-main">Prucalopride</span> Drug used to treat chronic constipation

Prucalopride, sold under brand names Resolor and Motegrity among others, is a medication acting as a selective, high affinity 5-HT4 receptor agonist which targets the impaired motility associated with chronic constipation, thus normalizing bowel movements. Prucalopride was approved for medical use in the European Union in 2009, in Canada in 2011, in Israel in 2014, and in the United States in December 2018. The drug has also been tested for the treatment of chronic intestinal pseudo-obstruction.

<span class="mw-page-title-main">Crofelemer</span> Pharmaceutical drug

Crofelemer is an antidiarrheal indicated for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. Other possible uses include diarrhea in children, acute infectious diarrhea, and diarrhea in patients with irritable bowel syndrome. It is a purified oligomeric proanthocyanidin from "dragon's blood", the sap of the South American tree Croton lechleri.

Dextromethorphan/quinidine, sold under the brand name Nuedexta, is a fixed-dose combination medication for the treatment of pseudobulbar affect (PBA). It contains dextromethorphan (DXM) and the class I antiarrhythmic agent quinidine.

<span class="mw-page-title-main">Eluxadoline</span> Chemical compound

Eluxadoline, sold under the brand names Viberzi and Truberzi, is a medication taken by mouth for the treatment of diarrhea and abdominal pain in individuals with diarrhea-predominant irritable bowel syndrome (IBS-D). It was approved for use in the United States in 2015. The drug originated from Janssen Pharmaceutica and was developed by Actavis.

<span class="mw-page-title-main">Olorinab</span> Chemical compound

Olorinab (APD371) is a drug being developed by Arena Pharmaceuticals for the treatment of gastrointestinal pain associated with Crohn's disease and irritable bowel syndrome. It acts as a potent and selective cannabinoid CB2 receptor agonist and is claimed to be orally active and peripherally selective. Initial Phase IIa exploratory clinical trials have been successful in patients with quiescent Crohn's disease. Arena initiated the Phase IIb Captivate trial in late July 2019 in patients with irritable bowel syndrome related pain, in constipation and diarrhea predominant sub-types. The Phase IIb trial is expected to enroll 240 participants between the ages of 18 and 70.Three doses of 10 mg, 25 mg, and 50 mg are being tested against Placebo in a 3:4 prescription ratio with a Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) masking layout.

References

  1. "Alverine capsules - Spasmonal, Audmonal. Side effects; dosage | Patient". Patient. Retrieved 2015-12-06.
  2. "Alverine Citrate Patient Information Leaflet" (PDF). Medicines.org.uk. 2014. Archived from the original (PDF) on 2017-12-01.
  3. Durakoğlu Z, Boztaş G, Sezgil A, Kaymakoğlu S, Dinçer D, Ozdil S, Beşişik F, Mungan Z, Okten A (December 2002). "Alverine induced toxic hepatitis: a case report" (PDF). The Turkish Journal of Gastroenterology. 13 (4): 226–8. PMID   16378311. Archived from the original (PDF) on 2018-11-23.
  4. Arhan M, Koklu S, Koksal AS, Yolcu OF, Koruk S, Koruk I, Kayacetin E (August 2004). "Alverine citrate induced acute hepatitis". World Journal of Gastroenterology. 10 (15): 2303–4. doi: 10.3748/wjg.v10.i15.2303 . PMC   4724969 . PMID   15259090.
  5. Coelho, A. M.; Jacob, L.; Fioramonti, J.; Bueno, L. (October 2001). "Rectal antinociceptive properties of alverine citrate are linked to antagonism at the 5-HT1A receptor subtype". The Journal of Pharmacy and Pharmacology. 53 (10): 1419–1426. doi:10.1211/0022357011777783. ISSN   0022-3573. PMID   11697552.
  6. "Detailed Info About Irritable bowel syndrome" . Retrieved 2017-07-26.
  7. "Alverine Citrate 60 mg Hard Capsules". Drugs.com. Retrieved 2015-12-06.
  8. Clinical trial number NCT00542295 for "Efficacy and Safety of Meteospasmyl® in Irritable Bowel Syndrome" at ClinicalTrials.gov
  9. Wittmann T, Paradowski L, Ducrotté P, Bueno L, Andro Delestrain MC (March 2010). "Clinical trial: the efficacy of alverine citrate/simeticone combination on abdominal pain/discomfort in irritable bowel syndrome--a randomized, double-blind, placebo-controlled study". Alimentary Pharmacology & Therapeutics. 31 (6): 615–24. doi: 10.1111/j.1365-2036.2009.04216.x . PMID   20003095. S2CID   35881469.
  10. "Alverine citrate 60 mg hard capsules - Summary of Product Characteristics (SPC) - (eMC)". www.medicines.org.uk. Retrieved 2015-12-06.